Single psilocybin dose eased depression for months, but not at one year

The question

Does a single dose of psilocybin, given with psychological support, reduce symptoms of major depression in the short term, and do any benefits last up to a year?

What they did

Researchers at a psychiatric clinic in Stockholm enrolled 35 adults with moderate to severe recurrent major depressive disorder between January 2021 and February 2024. Participants were randomly assigned to receive either a single 25 mg dose of psilocybin (17 people) or an active placebo of 100 mg niacin (18 people), a vitamin that causes noticeable physical effects but is not a psychedelic. Everyone also had five psychotherapeutic support sessions over 17 days. Neither participants nor raters knew who got what. Depression was measured with the clinician-rated MADRS scale at day 8 (the main outcome) and again at days 15, 42 and 365, plus monthly self-ratings.

What they found

On day 8, the psilocybin group improved more on the MADRS than the placebo group, by an estimated 7.27 points (95% CI, -12.89 to -1.65; P = .01). The gap remained at day 15 (11.03 points) and day 42 (8.33 points), but by day 365 the difference was 3.68 points and no longer statistically significant (P = .20). On the self-rated version, the psilocybin group was ahead as early as day 2 (9.58 points) and the difference persisted through day 102 (6.60 points), with only isolated differences later at days 283 and 343. Most side effects were short-lived and mild to moderate, and no drug-related serious adverse events were reported, but two people in the psilocybin group had persistent, severe anxiety that needed medical attention.

The fine print

The trial was small (35 people at one clinic), so estimates are imprecise, as the wide confidence intervals show. Psilocybin’s noticeable effects make blinding hard to maintain, even with an active placebo. The advantage over placebo faded by one year on the clinician-rated scale, and later self-report findings were scattered rather than consistent. This summary is based on the abstract alone.

What it means

In this small trial, one dose of psilocybin with psychological support was linked to faster and larger improvements in depression than an active placebo for about three months, but that advantage was no longer clear at one year, and a small number of people had lasting severe anxiety.

Evidence grade: Moderate. A double-blind randomized placebo-controlled trial with a long follow-up, but only 35 participants at a single clinic.

This summary is based on the study’s published abstract.